“Despite standard chemoradiotherapy (CRT), most women with lymph node (LN)–positive cervical cancer experience disease recurrence,” the authors explained. “Immunotherapy is being investigated in the up-front treatment setting.”
This was a prospective phase 1 study that took place in 29 Gynecology Oncology Cooperative Group member institutions. Patients were recruited between Dec. 18, 2012, and Aug. 31, 2016, and had a 14.8-month median follow-up and translational end points. A total of 34 patients with International Federation of Gynecology and Obstetrics stage IB2 to IVA cervical cancer with positive pelvic LNs, para-aortic LNs, or both were initially included in the study, and 13 were excluded because they did not receive ipilimumab. Eligible patients received six weekly doses of cisplatin 40 mg/m2 concurrently with radiotherapy. Following chemotherapy, patients received sequential ipilimumab every three weeks for four total doses; ipilimumab was administered in 3 mg/kg and 10 mg/kg doses to determine the maximum tolerated dose. The primary outcome measure was safety; other outcomes included overall and progression-free survival, and exploratory endpoints included human papillomavirus (HPV) genotype, HLA allele status, and PD-1 expression measured in peripheral blood.
There were 32 women in the intent-to-treat analysis, who had a median age of 50 (range, 26 to 61) years; most patients (n = 22, 69%) were white. Twenty-one women received ipilimumab, all of whom had positive pelvic LN; six (29%) had positive para-aortic LNs. All patients finished chemoradiotherapy to completion. The majority of women who received at least two ipilimumab cycles (n = 18, 86%) finished four ipilimumab cycles, and three (14%) completed two cycles. The maximum tolerated dose of ipilimumab was 10 mg/kg. the rate of self-limiting grade 3 toxic effects among the 21 ipilimumab patients was low (n = 2/21, 9.5%); these effects included lipase increase and dermatitis. Overall survival after 12 months was 90%, and progression-free survival was 81%. There were no correlations between HPV genotype and HLA subtype and progression-free or overall survival. PD-1-expresssing T cells were increased following chemoradiotherapy, and were sustained with ipilimumab.
“This study’s findings suggest that the use of immunotherapy after [chemoradiotherapy] for curative-intent treatment of patients with cervical cancer is tolerable and effective,” concluded the authors. “The results indicated that PD-1 was upregulated after [chemoradiotherapy] and sustained with sequential ipilimumab therapy. These immune findings may help guide future therapies to harness the activated T-cell phenotype in patients with node-positive cervical cancer.”